Courcelle Charmain T, Belle Jerilyn J, Courcelle Justin
Department of Biology, P.O. Box 751, Portland State University, Portland, OR 97207-0751, USA.
J Bacteriol. 2005 Oct;187(20):6953-61. doi: 10.1128/JB.187.20.6953-6961.2005.
Nucleotide excision repair and translesion DNA synthesis are two processes that operate at arrested replication forks to reduce the frequency of recombination and promote cell survival following UV-induced DNA damage. While nucleotide excision repair is generally considered to be error free, translesion synthesis can result in mutations, making it important to identify the order and conditions that determine when each process is recruited to the arrested fork. We show here that at early times following UV irradiation, the recovery of DNA synthesis occurs through nucleotide excision repair of the lesion. In the absence of repair or when the repair capacity of the cell has been exceeded, translesion synthesis by polymerase V (Pol V) allows DNA synthesis to resume and is required to protect the arrested replication fork from degradation. Pol II and Pol IV do not contribute detectably to survival, mutagenesis, or restoration of DNA synthesis, suggesting that, in vivo, these polymerases are not functionally redundant with Pol V at UV-induced lesions. We discuss a model in which cells first use DNA repair to process replication-arresting UV lesions before resorting to mutagenic pathways such as translesion DNA synthesis to bypass these impediments to replication progression.
核苷酸切除修复和跨损伤DNA合成是两个在停滞的复制叉处发挥作用的过程，以降低重组频率并促进紫外线诱导的DNA损伤后细胞的存活。虽然核苷酸切除修复通常被认为是无差错的，但跨损伤合成可能导致突变，因此确定决定每个过程何时被招募到停滞叉的顺序和条件很重要。我们在此表明，在紫外线照射后的早期，DNA合成的恢复是通过损伤的核苷酸切除修复发生的。在没有修复或细胞的修复能力被超过时，聚合酶V（Pol V）进行的跨损伤合成允许DNA合成恢复，并且是保护停滞的复制叉不被降解所必需的。聚合酶II和聚合酶IV对存活、诱变或DNA合成的恢复没有明显贡献，这表明在体内，这些聚合酶在紫外线诱导的损伤处与聚合酶V在功能上并非冗余。我们讨论了一个模型，即细胞首先利用DNA修复来处理阻止复制的紫外线损伤，然后才诉诸诱变途径，如如跨损伤DNA合成来绕过这些复制进展的障碍。
